RESUMO
Evidence has shown that women with type 2 diabetes mellitus (T2DM) have a greater risk of cardiovascular complications compared with men, but this sex difference is not clearly understood. This study assessed the microvascular function and circulatory biomarkers in postmenopausal women (PMW) with T2DM compared with diabetic men and their non-diabetic counterparts. Sixty participants were divided into nondiabetic PMW, PMW with T2DM, non-diabetic men, and diabetic men. Microvascular function was assessed using non-invasive equipment (EndoPAT®) and reported as reactive hyperemia index (RHI). Anthropometric and cardiovascular parameters were also measured. Two-way ANOVA was performed using sex (women or men) and T2DM (non-diabetic and diabetic) as the two factors. RHI impairment (1.97±0.14) was detected in diabetic PMW compared with women without T2DM (2.5±0.13) accompanied by lower adiponectin levels (T2DM: 9.3±1.2 and CTL: 13.8±1.8 ug/mL, P<0.05). An increase in the Nε-carboxymethyllysine (CML), nitrate/nitrite, and C-reactive protein (CRP) levels were observed in diabetic PMW compared to the other groups. Although a poor glycemia control was seen in diabetic men, neither RHI nor circulatory biomarkers were affected by T2DM. Multiple linear regression stratified by sex and T2DM identified some variables with RHI only in PMW with T2DM: HbA1c (P=0.003), body mass index (P=0.029), CML (P=0.032), and CRP (P=0.006). Diabetic PMW were more susceptible to the deleterious effects of hyperglycemia than men, showing microvascular dysfunction with high levels of pro-inflammatory mediators (CML and CRP) and a lower adiponectin concentration.
Assuntos
Diabetes Mellitus Tipo 2 , Anti-Inflamatórios , Biomarcadores , Índice de Massa Corporal , Diabetes Mellitus Tipo 2/complicações , Feminino , Humanos , Masculino , Pós-MenopausaRESUMO
Evidence has shown that women with type 2 diabetes mellitus (T2DM) have a greater risk of cardiovascular complications compared with men, but this sex difference is not clearly understood. This study assessed the microvascular function and circulatory biomarkers in postmenopausal women (PMW) with T2DM compared with diabetic men and their non-diabetic counterparts. Sixty participants were divided into nondiabetic PMW, PMW with T2DM, non-diabetic men, and diabetic men. Microvascular function was assessed using non-invasive equipment (EndoPAT®) and reported as reactive hyperemia index (RHI). Anthropometric and cardiovascular parameters were also measured. Two-way ANOVA was performed using sex (women or men) and T2DM (non-diabetic and diabetic) as the two factors. RHI impairment (1.97±0.14) was detected in diabetic PMW compared with women without T2DM (2.5±0.13) accompanied by lower adiponectin levels (T2DM: 9.3±1.2 and CTL: 13.8±1.8 ug/mL, P<0.05). An increase in the Nε-carboxymethyllysine (CML), nitrate/nitrite, and C-reactive protein (CRP) levels were observed in diabetic PMW compared to the other groups. Although a poor glycemia control was seen in diabetic men, neither RHI nor circulatory biomarkers were affected by T2DM. Multiple linear regression stratified by sex and T2DM identified some variables with RHI only in PMW with T2DM: HbA1c (P=0.003), body mass index (P=0.029), CML (P=0.032), and CRP (P=0.006). Diabetic PMW were more susceptible to the deleterious effects of hyperglycemia than men, showing microvascular dysfunction with high levels of pro-inflammatory mediators (CML and CRP) and a lower adiponectin concentration.
RESUMO
We aimed to present an overview of the literature regarding the interaction between physical exercise and APOE gene polymorphism on cognitive function, particularly in patients with Alzheimer's disease (AD). Firstly, this review focused on the effect of the physical exercise on cognitive function, regardless of APOE gene polymorphism. Some studies have shown that a high level of cardiorespiratory fitness is associated with less neuronal damage with an improvement in memory score tests whereas other studies failed to detect any association between physical exercise and cognitive improvement either in healthy individuals or patients with AD. Taken together, standardized protocols and more longitudinal studies are required to provide a better insight into the effects of physical exercise on cognitive function. Although there is no agreement in the literature regarding the effects of physical exercise on cognitive function, it is well established that it improves social interaction and the feeling of well-being, thereby positively contributing to the quality of life of the elderly. Regarding the influence of physical exercise on cognitive function in APOE ε4 allele carriers, the data trend shows that the carriers of allele ε4 for APOE gene were more responsive to the beneficial effects of physical exercise on cognitive function compared with non-carriers. Nevertheless, studies with larger sample sizes will provide more accuracy about this relationship.
Assuntos
Humanos , Idoso , Idoso de 80 Anos ou mais , Apolipoproteínas E/genética , Exercício Físico , Cognição , Polimorfismo Genético , Qualidade de Vida , Alelos , Doença de Alzheimer/genética , GenótipoRESUMO
We aimed to present an overview of the literature regarding the interaction between physical exercise and APOE gene polymorphism on cognitive function, particularly in patients with Alzheimer's disease (AD). Firstly, this review focused on the effect of the physical exercise on cognitive function, regardless of APOE gene polymorphism. Some studies have shown that a high level of cardiorespiratory fitness is associated with less neuronal damage with an improvement in memory score tests whereas other studies failed to detect any association between physical exercise and cognitive improvement either in healthy individuals or patients with AD. Taken together, standardized protocols and more longitudinal studies are required to provide a better insight into the effects of physical exercise on cognitive function. Although there is no agreement in the literature regarding the effects of physical exercise on cognitive function, it is well established that it improves social interaction and the feeling of well-being, thereby positively contributing to the quality of life of the elderly. Regarding the influence of physical exercise on cognitive function in APOE ε4 allele carriers, the data trend shows that the carriers of allele ε4 for APOE gene were more responsive to the beneficial effects of physical exercise on cognitive function compared with non-carriers. Nevertheless, studies with larger sample sizes will provide more accuracy about this relationship.
Assuntos
Apolipoproteínas E/genética , Cognição , Exercício Físico , Idoso , Idoso de 80 Anos ou mais , Alelos , Doença de Alzheimer/genética , Genótipo , Humanos , Polimorfismo Genético , Qualidade de VidaRESUMO
The health-promoting effects of exercise training (ET) are related to nitric oxide (NO) production and/or its bioavailability. The objective of this study was to determine whether single nucleotide polymorphism of the endothelial NO synthase (eNOS) gene at positions -786T>C, G894T (Glu298Asp) and at the variable number of tandem repeat (VNTR) Intron 4b/a would interfere with the cardiometabolic responses of postmenopausal women submitted to physical training. Forty-nine postmenopausal women were trained in sessions of 30-40 min, 3 days a week for 8 weeks. Genotypes, oxidative stress status and cardiometabolic parameters were then evaluated in a double-blind design. Both systolic and diastolic blood pressure values were significantly reduced after ET, which was genotype-independent. However, women without eNOS gene polymorphism at position -786T>C (TT genotype) and Intron 4b/a (bb genotype) presented a better reduction of total cholesterol levels (-786T>C: before = 213 ± 12.1, after = 159.8 ± 14.4, Δ = -24.9% and Intron 4b/a: before = 211.8 ± 7.4, after = 180.12 ± 6.4 mg/dL, Δ = -15%), and LDL cholesterol (-786T>C: before = 146.1 ± 13.3, after = 82.8 ± 9.2, Δ = -43.3% and Intron 4b/a: before = 143.2 ± 8, after = 102.7 ± 5.8 mg/dL, Δ = -28.3%) in response to ET compared to those who carried the mutant allele. Superoxide dismutase activity was significantly increased in trained women whereas no changes were observed in malondialdehyde levels. Women without eNOS gene polymorphism at position -786T>C and Intron 4b/a showed a greater reduction of plasma cholesterol levels in response to ET. Furthermore, no genotype influence was observed on arterial blood pressure or oxidative stress status in this population.
Assuntos
Exercício Físico/fisiologia , Óxido Nítrico Sintase Tipo III/genética , Polimorfismo de Nucleotídeo Único , Pós-Menopausa/genética , Pós-Menopausa/metabolismo , Pressão Sanguínea/fisiologia , Distribuição de Qui-Quadrado , Método Duplo-Cego , Feminino , Genótipo , Humanos , Lipídeos/sangue , Malondialdeído/sangue , Pessoa de Meia-Idade , Repetições Minissatélites/genética , Estresse Oxidativo/fisiologia , Fatores de TempoRESUMO
The health-promoting effects of exercise training (ET) are related to nitric oxide (NO) production and/or its bioavailability. The objective of this study was to determine whether single nucleotide polymorphism of the endothelial NO synthase (eNOS) gene at positions -786T>C, G894T (Glu298Asp) and at the variable number of tandem repeat (VNTR) Intron 4b/a would interfere with the cardiometabolic responses of postmenopausal women submitted to physical training. Forty-nine postmenopausal women were trained in sessions of 30-40 min, 3 days a week for 8 weeks. Genotypes, oxidative stress status and cardiometabolic parameters were then evaluated in a double-blind design. Both systolic and diastolic blood pressure values were significantly reduced after ET, which was genotype-independent. However, women without eNOS gene polymorphism at position -786T>C (TT genotype) and Intron 4b/a (bb genotype) presented a better reduction of total cholesterol levels (-786T>C: before = 213 ± 12.1, after = 159.8 ± 14.4, Δ = -24.9 percent and Intron 4b/a: before = 211.8 ± 7.4, after = 180.12 ± 6.4 mg/dL, Δ = -15 percent), and LDL cholesterol (-786T>C: before = 146.1 ± 13.3, after = 82.8 ± 9.2, Δ = -43.3 percent and Intron 4b/a: before = 143.2 ± 8, after = 102.7 ± 5.8 mg/dL, Δ = -28.3 percent) in response to ET compared to those who carried the mutant allele. Superoxide dismutase activity was significantly increased in trained women whereas no changes were observed in malondialdehyde levels. Women without eNOS gene polymorphism at position -786T>C and Intron 4b/a showed a greater reduction of plasma cholesterol levels in response to ET. Furthermore, no genotype influence was observed on arterial blood pressure or oxidative stress status in this population.
Assuntos
Feminino , Humanos , Pessoa de Meia-Idade , Exercício Físico/fisiologia , Óxido Nítrico Sintase Tipo III/genética , Polimorfismo de Nucleotídeo Único , Pós-Menopausa/genética , Pós-Menopausa/metabolismo , Pressão Sanguínea/fisiologia , Distribuição de Qui-Quadrado , Método Duplo-Cego , Genótipo , Lipídeos/sangue , Malondialdeído/sangue , Repetições Minissatélites/genética , Estresse Oxidativo/fisiologia , Fatores de TempoRESUMO
BACKGROUND AND PURPOSE: Obesity is associated with deterioration in asthma outcomes. Although airways eosinophil accumulation is characteristic of lung allergic diseases, little is known about the influence of obesity on the allergic eosinophil trafficking from bone marrow to lung tissues, and recruitment to airways lumen. Here, we have assessed the effects of diet-induced obesity on allergic eosinophilic inflammation in mice, examining eosinophil trafficking from bone marrow to airways, and production of T(H)1/T(H)2 cytokines. EXPERIMENTAL APPROACH: C57BL/6 mice fed for 10 weeks with standard chow or high-fat diet were sensitized and challenged with ovalbumin. At 24-96 h post-ovalbumin challenge, bronchoalveolar lavage (BAL) fluid, lung tissue and bone marrow were examined. KEY RESULTS: The high-fat-fed mice exhibited increased body weight and epididymal fat, glucose intolerance and alterations in lipid profile compared with the lean mice. Obesity markedly elevated serum leptin and lowered adiponectin levels. Ovalbumin challenge in obese mice promoted a markedly higher eosinophil accumulation in bone marrow and connective tissue surrounding the bronchial and bronchiolar segments. Eosinophil number in BAL fluid of obese mice was lower at 24 and 48 h. Levels of interleukin (IL)-5, eotaxin, tumour necrosis factor-alpha and IL-10 in BAL fluid of obese mice were significantly higher than in lean mice. CONCLUSIONS AND IMPLICATIONS: Diet-induced obesity enhanced eosinophil trafficking from bone marrow to lung tissues, and delayed their transit through the airway epithelium into the airway lumen. Consequently, eosinophils remain longer in lung peribronchiolar segments due to overproduction of T(H)1/T(H)2 cytokines and chemokines.
Assuntos
Asma/imunologia , Eosinófilos/imunologia , Pulmão/imunologia , Animais , Asma/patologia , Medula Óssea/imunologia , Brônquios/imunologia , Líquido da Lavagem Broncoalveolar/imunologia , Quimiocina CCL11 , Citocinas/biossíntese , Citocinas/imunologia , Citocinas/farmacologia , Eosinofilia/imunologia , Eosinofilia/patologia , Hipersensibilidade/imunologia , Hipersensibilidade/patologia , Inflamação/imunologia , Inflamação/patologia , Interleucina-10/imunologia , Interleucina-10/farmacologia , Interleucina-5/imunologia , Interleucina-5/farmacologia , Pulmão/efeitos dos fármacos , Pulmão/patologia , Pneumopatias/imunologia , Pneumopatias/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Obesidade/imunologia , Obesidade/patologia , Ovalbumina/imunologia , Ovalbumina/farmacologia , Pneumonia/imunologia , Pneumonia/patologia , Fator de Necrose Tumoral alfa/imunologia , Fator de Necrose Tumoral alfa/farmacologiaRESUMO
BACKGROUND AND PURPOSE: Overactive bladder is a complex and widely prevalent condition, but little is known about its physiopathology. We have carried out morphological, biochemical and functional assays to investigate the effects of long-term nitric oxide (NO) deficiency on muscarinic receptor and beta-adrenoceptor modulation leading to overactivity of rat detrusor muscle. EXPERIMENTAL APPROACH: Male Wistar rats received N(omega)-nitro-L-arginine methyl ester (L-NAME) in drinking water for 7-30 days. Functional responses to muscarinic and beta-adrenoceptor agonists were measured in detrusor smooth muscle (DSM) strips in Krebs-Henseleit solution. Measurements of [(3)H]inositol phosphate, NO synthase (NOS) activity, [(3)H]quinuclidinyl benzilate ([(3)H]QNB) binding and bladder morphology were also performed. KEY RESULTS: Long-term L-NAME treatment significantly increased carbachol-induced DSM contractile responses after 15 and 30 days; relaxing responses to the beta(3)-adrenoceptor agonist BRL 37-344 were significantly reduced at 30 days. Constitutive NOS activity in bladder was reduced by 86% after 7 days and maintained up to 30 days of L-NAME treatment. Carbachol increased sixfold the [(3)H]inositol phosphate in bladder tissue from rats treated with L-NAME. [(3)H]QNB was bound with an apparent K(D) twofold higher in bladder membranes after L-NAME treatment compared with that in control. No morphological alterations in DSM were found. CONCLUSIONS AND IMPLICATIONS: Long-term NO deficiency increased rat DSM contractile responses to a muscarinic agonist, accompanied by significantly enhanced K(D) values for muscarinic receptors and [(3)H]inositol phosphate accumulation in bladder. This supersensitivity for muscarinic agonists along with reductions of beta(3)-adrenoceptor-mediated relaxations indicated that overactive DSM resulted from chronic NO deficiency.
Assuntos
Contração Muscular/efeitos dos fármacos , Óxido Nítrico/deficiência , Receptores Adrenérgicos beta 3/metabolismo , Receptores Muscarínicos/metabolismo , Bexiga Urinária Hiperativa/fisiopatologia , Agonistas de Receptores Adrenérgicos beta 3 , Agonistas Adrenérgicos beta/farmacologia , Animais , Carbacol/farmacologia , Fosfatos de Inositol/metabolismo , Masculino , Agonistas Muscarínicos/farmacologia , Músculo Liso/metabolismo , NG-Nitroarginina Metil Éster , Óxido Nítrico Sintase/metabolismo , Ratos , Ratos Wistar , Receptores Muscarínicos/efeitos dos fármacos , Bexiga Urinária/metabolismo , Bexiga Urinária/fisiopatologiaRESUMO
Physical exercise reduces the deleterious effects of cardiovascular and inflammatory disorders. The purpose of the present study was to evaluate the beneficial effects of physical training on the inflammatory responses following lung ischaemia-reperfusion (IR) in rats. Male Wistar rats were divided into sham-operated animals and sedentary and trained animals submitted to lung IR. The run training programme consisted of 5 sessions.week(-1), each lasting 60 min.day(-1), at 66% of maximal oxygen consumption for 8 weeks. The left pulmonary artery, bronchus and pulmonary vein were occluded for 90 min and reperfused for 2 h. Lung protein extravasation was measured as (125)I-human albumin accumulation, whereas lung neutrophil infiltration was measured as myeloperoxidase activity. Lung IR in sedentary rats resulted in marked increases in protein extravasation and neutrophil influx, and in significant elevations of serum tumour necrosis factor (TNF)-alpha and interleukin (IL)-1beta levels. Physical preconditioning attenuated the increased IR-induced protein leakage without affecting neutrophil influx. It also reduced serum TNF-alpha (and IL-1beta) levels, but had no effect on IL-10 levels. Plasma superoxide dismutase activity was significantly increased in trained IR rats. The present data show that physical preconditioning protects the rat lung from ischaemia-reperfusion injury by attenuating the pulmonary vascular permeability that may be a consequence of reduced levels of tumour necrosis factor-alpha and interleukin-1beta and elevated superoxide dismutase activity.
Assuntos
Inflamação/prevenção & controle , Condicionamento Físico Animal , Traumatismo por Reperfusão/prevenção & controle , Síndrome do Desconforto Respiratório/prevenção & controle , Animais , Citocinas/metabolismo , Modelos Animais de Doenças , Masculino , Ratos , Ratos Wistar , Traumatismo por Reperfusão/patologia , CorridaRESUMO
The aim of this work was to evaluate the influence of run training on the responsiveness of corpus cavernosum (CC) from rats made hypertensive by treatment with nitric oxide (NO) synthesis inhibitor. Wistar rats were divided into sedentary control (C-SD), exercise training (C-TR), N(omega)-nitro-L-arginine methyl ester (L-NAME) sedentary (LN-SD) and L-NAME trained (LN-TR) groups. The run training program consisted in 8 weeks in a treadmill, 5 days/week, each session lasted 60 min. L-NAME treatment (2 and 10 mg/rat/day) started after 4 weeks of prior physical conditioning and lasted 4 weeks. Concentration-response curves were obtained for acetylcholine (ACh), sodium nitroprusside (SNP), sildenafil and BAY 41-2272. The effect of electrical field stimulation (EFS) on the relaxations responses of CC was evaluated. Run training prevented the arterial hypertension induced by L-NAME treatment (LN-SD: 135+/-2 and 141+/-2 mm Hg for both doses of L-NAME) compared to LN-SD groups (154+/-1 and 175+/-2 mm Hg, for 2 and 10 mg of L-NAME, respectively). Run training produced an increase in the maximal responses (E(max)) of CC for ACh (C-SD: 47+/-3; C-TR: 52+/-1; and LN-TR: 53+/-3%) and SNP (C-SD: 89+/-1; C-TR: 98+/-1; and LN-TR: 95+/-1%). Both potency and E(max) for ACh were reduced in a dose of 10 mg of L-NAME, and run training restored the reduction of E(max) for ACh. No changes were found for BAY 41-2271 and sildenafil. Relaxing responses to EFS was reduced by L-NAME treatment that was restored by prior physical conditioning. In conclusion, our study shows a beneficial effect of prior physical conditioning on the impaired CC relaxing responses in rats made hypertensive by chronic NO blockade.